Tamura S, Funato H, Hirabayashi Y, Suzuki Y, Nagamine T, Aizawa C, Kurata T
Department of Pathology, National Institute of Health, Tokyo, Japan.
Eur J Immunol. 1991 Jun;21(6):1337-44. doi: 10.1002/eji.1830210602.
Mice that were intranasally immunized with different influenza A virus hemagglutinins (HA), derived from PR8 (H1N1), A/Yamagata (H1N1) or A/Fukuoka (H3N2) virus, together with cholera toxin B subunit as an adjuvant, were examined for protection against PR8 infection; PR8 HA and A/Yamagata HA immunization conferred complete protection, while A/Fukuoka HA immunization failed to confer protection. In parallel with protection, PR8 HA-, A/Yamagata HA-, and A/Fukuoka HA-immunized mice produced a high, a moderate and a low level of PR8 HA-reactive IgA in the respiratory tract, respectively. These IgA antibodies were not only higher in content in the nasal secretions, but also more cross-reactive than IgG. The purified IgA antibodies from respiratory tract washings of PR8 HA-immunized mice, which contained the HA-specific IgA corresponding to the amount detected in the nasal wash, were able to protect mice from PR8 challenge when transferred to the respiratory tract of naive mice. The transfer of IgA from A/Yamagata HA-immunized mice also afforded cross-protection against PR8 infection, whereas the IgA from A/Fukuoka HA-immunized mice failed to provide protection. The ability of transferred IgA to prevent viral infection was dependent on the amount of HA-reactive IgA remaining in the respiratory tract of the host at the time of infection. These experiments directly demonstrate that IgA antibodies to influenza A virus HA by themselves play a pivotal role in defence not only against homologous virus infection, but also against heterologous drift virus infection at the respiratory mucosa, the portal of entry for the viruses.
将源自PR8（H1N1）、A/山形（H1N1）或A/福冈（H3N2）病毒的不同甲型流感病毒血凝素（HA）与霍乱毒素B亚基作为佐剂一起经鼻内免疫小鼠后，检测其对PR8感染的保护作用；PR8 HA和A/山形HA免疫可提供完全保护，而A/福冈HA免疫未能提供保护。与保护作用平行的是，经PR8 HA、A/山形HA和A/福冈HA免疫的小鼠在呼吸道中分别产生了高水平、中等水平和低水平的PR8 HA反应性IgA。这些IgA抗体不仅在鼻分泌物中的含量更高，而且比IgG具有更强的交叉反应性。从经PR8 HA免疫的小鼠呼吸道冲洗液中纯化的IgA抗体，其含有的HA特异性IgA与鼻冲洗液中检测到的量相当，当转移到未免疫小鼠的呼吸道时，能够保护小鼠免受PR8攻击。从经A/山形HA免疫的小鼠转移的IgA也能提供针对PR8感染的交叉保护，而从经A/福冈HA免疫的小鼠转移的IgA则不能提供保护。转移的IgA预防病毒感染的能力取决于感染时宿主呼吸道中残留的HA反应性IgA的量。这些实验直接证明，针对甲型流感病毒HA的IgA抗体自身不仅在抵御同源病毒感染中起关键作用，而且在呼吸道黏膜（病毒的进入门户）抵御异源漂移病毒感染中也起关键作用。
